Circadian clocks in fuel harvesting and energy homeostasis.

Circadian systems have evolved in plants, eubacteria, neurospora, and the metazoa as a mechanism to optimize energy acquisition and storage in synchrony with the rotation of the Earth on its axis. In plants, circadian clocks drive the expression of genes involved in oxygenic photosynthesis during the light and nitrogen fixation during the dark, repeating this cycle each day. In mammals, the core clock in the suprachiasmatic nucleus (SCN) functions to entrain extra-SCN and peripheral clocks to the light cycle, including regions central to energy homeostasis and sleep, as well as peripheral tissues involved in glucose and lipid metabolism. Tissue-specific gene targeting has shown a primary role of clock genes in endocrine pancreas insulin secretion, indicating that local clocks play a cell-autonomous role in organismal homeostasis. A present focus is to dissect the consequences of clock disruption on modulation of nuclear hormone receptor signaling and on posttranscriptional regulation of intermediary metabolism. Experimental genetic studies have pointed toward extensive interplay between circadian and metabolic systems and offer a means to dissect the impact of local tissue molecular clocks on fuel utilization across the sleep-wake cycle.